leukotriene b4
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Foods ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 184
Hongying Cai ◽  
Zhiguo Wen ◽  
Xin Xu ◽  
Jiaxin Wang ◽  
Xuan Li ◽  

Lactobacillus plantarum is considered a potential probiotic supplementation for treating obesity. However, the underlying molecular mechanism is poorly understood. Our previous study displayed that L. plantarum FRT4 alleviated obesity in mice fed a high-fat diet (HFD) through ameliorating the HFD-induced gut microbiota dysbiosis. To explore the roles of FRT4 in obesity prevention, in this study, we investigated changes in serum metabolomic phenotype by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and analyzed the pathway of HFD-fed Kunming female mice orally administered with FRT4 for eight weeks. Using orthogonal partial least squares discriminant analysis (OPLS-DA), metabolite patterns with significant changes were observed. 55 metabolites including phosphatidylcholine, lysophophatidylcholine, sphingomyelin, serotonin, indole-3-methyl aceta, indole-3-carbinol, indole-5,6-quino, 11,12-DHET, prostaglandin B2, leukotriene B4, and 3-hydroxybenzoic acid were identified as potential biomarkers associated with obesity, which were mainly involving in glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. Perturbations of 14 biomarkers could be regulated by FRT4 intervention. These metabolites may serve as valuable biomarkers to understand the mechanisms by which intake of diets containing FRT4 contributes to the treatment or prevention of obesity. Thus, FRT4 can be a promising dietary supplement for the prevention of HFD-induced obesity.

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Jing Luo ◽  
Qingjie Ma ◽  
Heng Tang ◽  
Xi Zou ◽  
Xin Guo ◽  

Background. Mechanical ventilation (MV) can provoke acute lung injury (ALI) by increasing inflammation activation and disrupting the barrier in lung tissues even causing death. However, the inflammation-related molecules and pathways in MV-induced ALI remain largely unknown. Hence, the purposes of this study are to examine the role and mechanism of a novel inflammation-related molecule, leukotriene B4 (LTB4), in ALI. Methods. The functions of LTB4 in one-lung ventilation (OLV) model were detected by the loss-of-function experiments. H&E staining was used to examine the pathologic changes of lung tissues. Functionally, PLCε-1 knockdown and Toll-like receptor 4 (TLR4)/NF-κB pathway inhibitor were used to detect the regulatory effects of LTB4 on the phospholipase Cε (PLCε-1)/TLR4/nuclear factor-kappa B (NF-κB) pathway. The levels of genes and proteins were determined by RT-qPCR and western blotting assay. The levels of inflammation cytokines and chemokines were measured by ELISA. Results. Here, we found LTA4H, leukotriene B (4) receptor 1 (BLT1), LTB4, and PLCε-1 upregulated in OLV rats and associated with inflammatory activation and lung permeability changes of lung tissues. Inhibition of LTB4 alleviated the OLV-induced ALI by inhibiting inflammatory activation and lung permeability changes of lung tissues. For mechanism analyses, LTB4 promoted OLV-induced ALI by activating the PLCε-1/TLR4/NF-κB pathway. Conclusion. LTB4 induced ALI in OLV rats by activating the PLCε-1/TLR4/NF-κB pathway. Our findings might supply a new potential therapeutic for OLV-induced ALI.

Jan Heering ◽  
Victor Hernandez-Olmos ◽  
Niklas Ildefeld ◽  
Ting Liu ◽  
Anja Kaiser ◽  

2022 ◽  
Vol 12 ◽  
Yuze Yuan ◽  
Chao Wang ◽  
Guoqiang Wang ◽  
Xiaoping Guo ◽  
Shengyu Jiang ◽  

Allergic rhinitis (AR) is a common heterogeneous chronic disease with a high prevalence and a complex pathogenesis influenced by numerous factors, involving a combination of genetic and environmental factors. To gain insight into the pathogenesis of AR and to identity diagnostic biomarkers, we combined systems biology approach to analyze microbiome and serum composition. We collected inferior turbinate swabs and serum samples to study the microbiome and serum metabolome of 28 patients with allergic rhinitis and 15 healthy individuals. We sequenced the V3 and V4 regions of the 16S rDNA gene from the upper respiratory samples. Metabolomics was used to examine serum samples. Finally, we combined differential microbiota and differential metabolites to find potential biomarkers. We found no significant differences in diversity between the disease and control groups, but changes in the structure of the microbiota. Compared to the HC group, the AR group showed a significantly higher abundance of 1 phylum (Actinobacteria) and 7 genera (Klebsiella, Prevotella and Staphylococcus, etc.) and a significantly lower abundance of 1 genus (Pelomonas). Serum metabolomics revealed 26 different metabolites (Prostaglandin D2, 20-Hydroxy-leukotriene B4 and Linoleic acid, etc.) and 16 disrupted metabolic pathways (Linoleic acid metabolism, Arachidonic acid metabolism and Tryptophan metabolism, etc.). The combined respiratory microbiome and serum metabolomics datasets showed a degree of correlation reflecting the influence of the microbiome on metabolic activity. Our results show that microbiome and metabolomics analyses provide important candidate biomarkers, and in particular, differential genera in the microbiome have also been validated by random forest prediction models. Differential microbes and differential metabolites have the potential to be used as biomarkers for the diagnosis of allergic rhinitis.

Yue Wang ◽  
Xuemei Nan ◽  
Yiguang Zhao ◽  
Linshu Jiang ◽  
Hui Wang ◽  

Milk microbiota and mediated metabolites directly affect the health of the udder in dairy cows. Inulin, a dietary prebiotic, can modulate the profile of gastrointestinal microbiota. However, whether the inulin intake affects the milk microbial population and metabolites remains unknown. In this study, forty subclinical mastitis (SCM) cows were randomly divided into 5 groups. Five inulin addition doses, 0, 100, 200, 300 and 400 g/d per cow, based on the same basal diet were supplemented, respectively. The experiments lasted for 8 weeks. The results showed lower relative abundance of mastitic-causing and pro-inflammation microbes in milk (i.e., Escherichia -Shigella , Pseudomonas , Rhodococcus and Burkholderia-Caballeronia-Paraburkholderia , etc.), and higher probiotics and commensal bacteria, such as, Lactobacillus , Bifidobacterium , etc. in the cows fed 300 g/d inulin, compared with the control group. Meanwhile, the levels of arachidonic acid pro-inflammatory mediators (leukotriene E3, 20-carboxy-leukotriene B4 and 12-Oxo-c-LTB3) and phospholipid metabolites were reduced, and the levels of compounds with antibacterial and anti-inflammatory potential (prostaglandin A1 and 8-iso-15-Keto-PGE 2 , etc.), and participating energy metabolism (citric acid and L-Carnitine, etc.) were elevated. These data suggested that inulin intake might modulate the microflora and metabolites level in extra-intestinal tissue, such as mammary gland, which provided an alternative for the regulation and mitigation for SCM. IMPORTANCE The profile of microbial community and metabolic activity in milk are main determinant of udder health status and milk quality. Recent studies have demonstrated that diet could directly modulate mammary gland microbiome. Inulin is a probiotic dietary fiber, which can improve the microbiota population in gastrointestinal tract. However, whether inulin intake can further regulate the profile of microbiota and metabolic activities in milk remains unclear. In subclinical mastitic cows, we found that inulin supplementation could reduce the abundance of Escherichia -Shigella , Pseudomonas , Rhodococcus , Burkholderia-Caballeronia-Paraburkholderia and the levels of (±)12, 13 - DiHOME, leukotriene E3 and 20-Carboxy-Leukotriene B4 etc., while, elevated the abundance of Lactobacillus , Bifidobacterium , and Muribaculaceae as well as the levels of prostaglandin A1 (PGA1), 8-iso-15-keto-PGE2 and benzoic acid etc., in milk. These data suggest that inulin intake affects the profile of microorganisms and metabolites in milk, which provides an alternative for the regulation of mastitis.

Kyung Wook Heo ◽  
Kwang Pak ◽  
Arwa Kurabi ◽  
Allen F. Ryan

BackgroundPathogens of otitis media (OM) induce inflammatory responses in the middle ear (ME), characterized by mucosal hyperplasia, leukocyte infiltration, and inflammatory mediators, including arachidonic acid metabolites. We studied the role of the eicosanoid leukotriene B4 (LTB4) in OM.MethodsExpression of LTB4-related genes was evaluated by gene array and single-cell RNA-Seq in MEs infected with nontypeable Haemophilus influenzae (NTHi). An inhibitor of LTB4 receptor 1 (i.e. U75302) was also used to block LTB4 responses.ResultsME expression of LTB4-related genes was observed by gene arrays and scRNA-Seq. However, not all genes involved in LTB4 generation occurred in any one specific cell type. Moreover, LTB4 receptor inhibition significantly reduced mucosal hyperplasia and virtually eliminated leukocyte infiltration.ConclusionsME expression of LTB4-related genes suggest a functional role in OM disease. The fact that LTB4-generation is spread across different cell types is consistent with a transcellular pathway of eicosanoid biosynthesis involving cell-to-cell signaling as well as transfer of biosynthetic intermediates between cells. The dramatic reduction in ME leukocyte infiltration caused by U75302 indicates that LTB4 plays a major role in ME inflammatory cell recruitment, acting via the LTB4R1 receptor. Given that there are many other chemotactic factors that occur in the ME during OM, the ability of LTB4 to activate leukocytes and stimulate their extravasation may explain the effects of inhibition. Reduction in mucosal hyperplasia due to U75302 administration may be secondary to the reduction in leukocytes since LTB4R1 is not expressed by mucosal epithelial or stromal cells. The results suggest that LTB4 receptor antagonists could be useful in treating OM.

Yiyi Gong ◽  
Xiaolin Ni ◽  
Chenxi Jin ◽  
Xiang Li ◽  
Yujie Wang ◽  

Abstract Context Excessive production of fibroblast growth factor 23 (FGF23) by tumor was considered as the main pathogenesis in tumor-induced osteomalacia (TIO). Despite its importance to comprehensive understanding of pathogenesis and diagnosis, the regulation of systemic metabolism in TIO remains unclear. Objectives We aimed to systematically characterize the metabolome alteration associated with TIO. Methods By means of liquid chromatography-tandem mass spectrometry (LC-MS) based metabolomics, we analyzed the metabolic profile from 96 serum samples (32 initial diagnosis TIO patients, pairwise samples after tumor resection and 32 matched healthy control subjects). In order to screen and evaluate potential biomarkers, statistical analyses, pathway enrichment and receiver operating characteristic (ROC) were performed. Results Metabolomic profiling revealed distinct alterations between TIO and HC cohort. Differential metabolites were screened and conducted to functional clustering and annotation. Significantly enriched pathway was found involved in arachidonic acid metabolism. A combination of 5 oxylipins, 4-HDoHE, leukotriene B4, 5-HETE, 17-HETE and 9,10,13-TriHOME, demonstrated a high sensitivity and specificity panel for TIO prediction screened by random forest (RF) algorithm (AUC=0.951, 95% confidence interval, CI 0.827-1). Supported vector machine (SVM) model and partial least-squares (PLS) model were conducted to validate the predictive capabilities of the diagnostic panel. Conclusions Metabolite profiling of TIO altered significant compared with HC. A high sensitivity and specificity panel with 5 oxylipins were tested as diagnostic predictor. For the first time, we provide the global profile of metabolomes and identify potential diagnostic biomarkers of TIO. The present work may offer novel insights into the pathogenesis of TIO.

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1873
Undurti N Das

Arachidonic acid (AA) metabolism is critical in the initiation and resolution of inflammation. Prostaglandin E2 (PGE2) and leukotriene B4/D4/E4 (LTB4/LD4/LTE4), derived from AA, are involved in the initiation of inflammation and regulation of immune response, hematopoiesis, and M1 (pro-inflammatory) macrophage facilitation. Paradoxically, PGE2 suppresses interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production and triggers the production of lipoxin A4 (LXA4) from AA to initiate inflammation resolution process and augment regeneration of tissues. LXA4 suppresses PGE2 and LTs’ synthesis and action and facilitates M2 macrophage generation to resolve inflammation. AA inactivates enveloped viruses including SARS-CoV-2. Macrophages, NK cells, T cells, and other immunocytes release AA and other bioactive lipids to produce their anti-microbial actions. AA, PGE2, and LXA4 have cytoprotective actions, regulate nitric oxide generation, and are critical to maintain cell shape and control cell motility and phagocytosis, and inflammation, immunity, and anti-microbial actions. Hence, it is proposed that AA plays a crucial role in the pathobiology of ischemia/reperfusion injury, sepsis, COVID-19, and other critical illnesses, implying that its (AA) administration may be of significant benefit in the prevention and amelioration of these diseases.

Linlin Feng ◽  
Fengyan Sun ◽  
Yan Chen ◽  
Seyyed Shamsadin Athari ◽  
Xiaoyun Chen

  Allergic asthma is a complex lung disease characterized by breathlessness, airway inflammation, and obstruction. Allergy and allergic rhinitis (AR) are the main triggers of asthma. Vitamin A is an important supplementary factor for the physiological activation of the immune system. In the present study, we investigated the effects of vitamin A on the exacerbation of allergic asthma symptoms. BALB/c mice were allocated to four groups. Asthma was created in two groups, and in the other two groups, rhinitis was induced. One of the asthma groups and one of the rhinitis groups orally received vitamin A (20 IU/g for 15 days). The levels of Immunoglobulin (Ig) E, histamine, leukotriene B4 (LTB4), Cysteinyl leukotriene receptor (Cys-LT), interleukin (IL)-4, IL-5, IL-13, and IL-35 as well as eosinophil peroxidase activity, were measured. Also, the histopathology of mice lungs was evaluated. The levels of total IgE, LTB4, Cys-LT, IL-4, IL-5, IL-17, and IL-33, eosinophil peroxidase activity, perivascular and peribronchial inflammation significantly decreased in vitamin A-treated asthma and rhinitis groups compared to non-treated groups. Also, IL-13 and histamine levels, hyperplasia of the goblet cell, and hyper-secretion of the mucus insignificantly decreased in vitamin A-treated asthma and rhinitis groups. Asthma and AR are common diseases that are generally developed due to the dysregulation of the immune system. Vitamin A plays an important role in controlling the immunopathologic mechanisms of allergic diseases. Vitamin A could be a useful supplement in managing AR and asthma by decreasing the severity of inflammatory responses. Therefore, control of vitamin A deficiency is recommended in Allergy.

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